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Wrapping Up the Axon

The regulation of myelin sheath thickness is extremely important for neural function because it regulates nerve conduction velocity. Myelin thickness is proportional to axon size--small axons have little myelin, whereas large-caliber axons have a thick myelin sheath. Schwann cells deliver the correct number of myelin wraps, but how do Schwann cells "sense" the diameter of the engulfed axon? Michailov et al. (see the cover and the Perspective by ffrench-Constant et al.) now suggest that Schwann cells respond to an axonal growth factor, neuregulin-1, and integrate this cell surface signal to create a biochemical measure of axon caliber. Altering the extent of neuregulin-1 signaling alters myelin thickness, and reduced neuregulin-1 gene dosage in mice "misleads" the Schwann cell as to the true caliber of the axonal segment, which results in reduced myelination and slowing of nerve conduction velocity.